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1、PowerComparisonofStatisticalTestsofAssociationwithMultipleSNPswiththeGAW16RheumatoidArthritisDataWeiZhong,WeiPan§DivisionofBiostatistics,SchoolofPublicHealth,UniversityofMinnesota,Minneapolis,MN55455§CorrespondingauthorEmailaddresses:WeiPan:weip@biostat.umn.eduAbstractDuetoweakassociation
2、strengthsbetweencomplextraitsandcausalDNAvariants,itisimportanttoevaluatestatisticalpowerofanytestingenome-wideassociationstudies.Inthispaper,weconsidersomewell-knownornewlyclaimedwinnersofsingle-locusandmultilocustestsasappliedtoablockofSNPs,possiblyinlinkagedisequilibrium(LD),forthecase
3、-controlstudydesign.TakingadvantageofthelargesamplesizeoftheGAW16RheumatoidArthritis(RA)dataandseveralwell-establishedRA-associatedgenesorchromosomeregions,weuserepeatedsubsamplesofthedatatoestimatethepowerandthuscomparetheperformanceofthetestsunderpracticalsituations.Theresultsconfirmthe
4、well-knownfactthattheredoesnotexistauniformlymostpowerfultestacrossallscenarios.Hence,werecommendtheuseofmultipletests,includingtheunivariatesingle-locustestandfourmultilocustests:theSumtest,amultivariateglobaltest(e.g.thescoretest),theSumSqUandSumSqUwtests.BackgroundGiventhatmostcomplexd
5、iseasesortraitsareonlyweaklyassociatedwithcausalDNAvariants,thestatisticalpowerofatestbeingusedtoanalyzegenome-wideassociation(GWA)dataiscritical.Inthispaper,weconsidersomewell-knownornewlyclaimedwinnersofsingle-locusormultilocustestsasappliedtomultipleSNPs,e.g.,inaslidingwindoworinalinka
6、gedisequilibrium(LD)block,forthecase-controlstudydesign.AveryrecentstudybyChapmanandWhittaker(2008)indicatedthataunivariatetestoranempiricalBayestestproposedbyGoemanetal(2006)wasoftenmostpowerfulamongseveralcommonlyusedtestsacrossarangeofscenarios;inparticular,theyweremorepowerfulthanaso-
7、calledSumtestthatisequivalenttoregressingtheresponse(i.e.diseasestatus)onthesumofthecodedSNPs,andthanaweightedscoretest(WST)(WangandElston2007);however,theydidnotconsidersimulationset-upsofWangandElston(2007),whichwasconsideredbyPan(2008).Pan'sresultsindicatedthatun
